Differences in the neural correlates of schizophrenia with positive and negative formal thought disorder in patients with schizophrenia in the ENIGMA dataset.

Formal thought disorder (FTD) is a clinical key factor in schizophrenia, but the neurobiological underpinnings remain unclear. In particular, the relationship between FTD symptom dimensions and patterns of regional brain volume loss in schizophrenia remains to be established in large cohorts. Even less is known about the cellular basis of FTD. Our study addresses these major obstacles by enrolling a large multi-site cohort acquired by the ENIGMA Schizophrenia Working Group (752 schizophrenia patients and 1256 controls), to unravel the neuroanatomy of FTD in schizophrenia and using virtual histology tools on implicated brain regions to investigate the cellular basis. Based on the findings of previous clinical and neuroimaging studies, we decided to separately explore positive, negative and total formal thought disorder. We used virtual histology tools to relate brain structural changes associated with FTD to cellular distributions in cortical regions. We identified distinct neural networks positive and negative FTD. Both networks encompassed fronto-occipito-amygdalar brain regions, but positive and negative FTD demonstrated a dissociation: negative FTD showed a relative sparing of orbitofrontal cortical thickness, while positive FTD also affected lateral temporal cortices. Virtual histology identified distinct transcriptomic fingerprints associated for both symptom dimensions. Negative FTD was linked to neuronal and astrocyte fingerprints, while positive FTD also showed associations with microglial cell types. These results provide an important step towards linking FTD to brain structural changes and their cellular underpinnings, providing an avenue for a better mechanistic understanding of this syndrome.

Neurofilament light chain concentration mediates the association between regional medial temporal lobe structure and memory in adults with Down syndrome.

INTRODUCTION: Virtually all people with Down syndrome (DS) develop neuropathology associated with Alzheimer's disease (AD). Atrophy of the hippocampus and entorhinal cortex (EC), as well as elevated plasma concentrations of neurofilament light chain (NfL) protein, are markers of neurodegeneration associated with late-onset AD. We hypothesized that hippocampus and EC gray matter loss and increased plasma NfL concentrations are associated with memory in adults with DS. METHODS: T1-weighted structural magnetic resonance imaging (MRI) data were collected from 101 participants with DS. Hippocampus and EC volume, as well as EC subregional cortical thickness, were derived. In a subset of participants, plasma NfL concentrations and modified Cued Recall Test scores were obtained. Partial correlation and mediation were used to test relationships between medial temporal lobe (MTL) atrophy, plasma NfL, and episodic memory. RESULTS: Hippocampus volume, left anterolateral EC (alEC) thickness, and plasma NfL were correlated with each other and were associated with memory. Plasma NfL mediated the relationship between left alEC thickness and memory as well as hippocampus volume and memory. DISCUSSION: The relationship between MTL gray matter and memory is mediated by plasma NfL levels, suggesting a link between neurodegenerative processes underlying axonal injury and frank gray matter loss in key structures supporting episodic memory in people with DS.

Pathways linking pulse pressure to dementia in adults with Down syndrome.

Individuals with Down syndrome (DS) are less likely to have hypertension than neurotypical adults. However, whether blood pressure measures are associated with brain health and clinical outcomes in this population has not been studied in detail. Here, we assessed whether pulse pressure is associated with markers of cerebrovascular disease, entorhinal cortical atrophy, and diagnosis of dementia in adults with DS. Participants with DS from the Biomarkers of Alzheimer's Disease in Adults with Down Syndrome study (ADDS; n=195, age=50.6±7.2 years, 44% women, 18% diagnosed with dementia) were included. Higher pulse pressure was associated with greater global, parietal, and occipital WMH volume. Pulse pressure was not related to enlarged PVS, microbleeds, infarcts, entorhinal cortical thickness, or dementia diagnosis. However, in a serial mediation model, we found that pulse pressure was indirectly related to dementia diagnosis through parieto-occipital WMH and, subsequently through entorhinal cortical thickness. Higher pulse pressure may be a risk factor for dementia in people with DS by promoting cerebrovascular disease, which in turn affects neurodegeneration. Pulse pressure is an important determinant of brain health and clinical outcomes in individuals with Down syndrome despite the low likelihood of frank hypertension.

Neural Correlates of Positive and Negative Formal Thought Disorder in Individuals with Schizophrenia: An ENIGMA Schizophrenia Working Group Study.

Formal thought disorder (FTD) is a key clinical factor in schizophrenia, but the neurobiological underpinnings remain unclear. In particular, relationship between FTD symptom dimensions and patterns of regional brain volume deficiencies in schizophrenia remain to be established in large cohorts. Even less is known about the cellular basis of FTD. Our study addresses these major obstacles based on a large multi-site cohort through the ENIGMA Schizophrenia Working Group (752 individuals with schizophrenia and 1256 controls), to unravel the neuroanatomy of positive, negative and total FTD in schizophrenia and their cellular bases. We used virtual histology tools to relate brain structural changes associated with FTD to cellular distributions in cortical regions. We identified distinct neural networks for positive and negative FTD. Both networks encompassed fronto-occipito-amygdalar brain regions, but negative FTD showed a relative sparing of orbitofrontal cortical thickness, while positive FTD also affected lateral temporal cortices. Virtual histology identified distinct transcriptomic fingerprints associated for both symptom dimensions. Negative FTD was linked to neuronal and astrocyte fingerprints, while positive FTD was also linked to microglial cell types. These findings relate different dimensions of FTD to distinct brain structural changes and their cellular underpinnings, improve our mechanistic understanding of these key psychotic symptoms.

Frequency of Medical Claims for Diastasis Recti Abdominis Among U.S. Active Duty Service Women, 2016 to 2019.

Background: Diastasis recti abdominis (DRA) is a condition in pregnant and postpartum women. Proposed risk factors include age, sex, multiparity, cesarean delivery, diabetes, gestational weight gain, and high birth weight. This study aims to estimate the prevalence of DRA using medical claims data among U.S. active duty service women (ADSW) and determine associated risk factors. Materials and Methods: We conducted a cross-sectional study of ADSW aged 18 years and older in the U.S. Army, Air Force, Navy, and Marine Corps during fiscal years (FYs) 2016 to 2019. Utilizing claims data, we identified ADSW with a diagnosis of DRA during the study period. Risk factors, including age, race, socioeconomic status, branch of service, military occupation, delivery type, and parity, were evaluated through descriptive statistics, chi-square tests, and logistic regression analysis. Results: A total of 340,748 ADSW were identified during FYs 2016 to 2019, of whom 2,768 (0.81%) had a medical claim for DRA. Of those with deliveries during the study period, 1.41% were multiparous and 84.53% had a cesarean delivery. Increased risk of DRA was found in ages 30 to 39 years, Black women, ranks representing a higher socioeconomic status, and women with overweight and obese body mass indices. Conclusions: Although the prevalence of DRA, defined as a medical claim for DRA, in the study population is low, subpopulations may be disproportionately affected by the condition. Further research could potentially detail the impact of DRA on the functional impairment and operational readiness of ADSW in the U.S. military and any possible means of prevention.

Neural Correlates of Positive and Negative Formal Thought Disorder in Individuals with Schizophrenia: An ENIGMA Schizophrenia Working Group Study.

Formal thought disorder (FTD) is a key clinical factor in schizophrenia, but the neurobiological underpinnings remain unclear. In particular, relationship between FTD symptom dimensions and patterns of regional brain volume deficiencies in schizophrenia remain to be established in large cohorts. Even less is known about the cellular basis of FTD. Our study addresses these major obstacles based on a large multi-site cohort through the ENIGMA Schizophrenia Working Group (752 individuals with schizophrenia and 1256 controls), to unravel the neuroanatomy of positive, negative and total FTD in schizophrenia and their cellular bases. We used virtual histology tools to relate brain structural changes associated with FTD to cellular distributions in cortical regions. We identified distinct neural networks for positive and negative FTD. Both networks encompassed fronto-occipito-amygdalar brain regions, but negative FTD showed a relative sparing of orbitofrontal cortical thickness, while positive FTD also affected lateral temporal cortices. Virtual histology identified distinct transcriptomic fingerprints associated for both symptom dimensions. Negative FTD was linked to neuronal and astrocyte fingerprints, while positive FTD was also linked to microglial cell types. These findings relate different dimensions of FTD to distinct brain structural changes and their cellular underpinnings, improve our mechanistic understanding of these key psychotic symptoms.

Female Family Physicians Are More Racially Diverse Than Their Male Counterparts in Federal Sites.

Supporting a diverse family physician workforce is an integral component of achieving health equity. This study compared the racial/ethnic composition of Federal family physicians (Military, Veterans Administration/Department of Defense) to the entire cohort of family physicians and stratified by gender. Female family physicians serving at Federal sites were more diverse than the overall population of female family physicians and, also than their male Federal counterparts. This gendered trend among Federal physicians needs further exploration.

Obesity Risk Among West Point Graduates Later in Life.

ABSTRACT: Szivak, TK, Thomas, MM, Pietrzak, RH, Nguyen, DR, Ryan, DM, and Mazure, CM. Obesity Risk Among West Point Graduates Later in Life. J Strength Cond Res 37(6): 1284-1291, 2023-The purpose of this investigation was to evaluate sex differences in health and fitness outcomes among United States Military Academy (USMA) graduates (class years 1980-2011). Subjects ( n = 701 men, 641 women, age: 45.7 ± 9.3 years) were surveyed as a part of a larger investigation on risk and resiliency factors among USMA graduates. Physical activity was assessed using the International Physical Activity Questionnaire (IPAQ) short form and calculation of weekly metabolic equivalents (METs). Overweight and obesity status were assessed by body mass index (BMI). Significance for the study was set at p ≤ 0.05. Obesity rates for men (30.1%) were significantly higher than for women (16.6%). Men reported significantly higher ( p = 0.01) vigorous METs·wk -1 (1,214.6 ± 1,171.6) than women (1,046.8 ± 1,133.2) despite significantly higher ( p = 0.00) BMI values (28.75 ± 4.53 kg·m -2 ) than women (25.90 ± 5.48 kg·m -2 ). Women were 89% more likely to have ever been on a diet and reported higher (15.2%) Army Body Composition Program enrollment rates than men (6.3%). Obesity rates among men reflect trends seen in the broader military, Veteran, and U.S. adult populations, whereas obesity rates among women were lower. Men may be at a greater risk for obesity later in life despite higher self-reported physical activity; however, lean body mass and self-report bias should be considered. Because lifetime obesity may be influenced by factors other than physical activity, health initiatives should use a comprehensive approach early in the career of military officers.

Free the Bun: Prevalence of Alopecia Among Active Duty Service Women, Fiscal Years 2010-2019.

INTRODUCTION: Active duty service women (ADSW) constitute 16% of the force. The prevalence of alopecia, a dermatologic condition characterized by hair loss, is understudied in regard to hairstyle regulations across the U.S. military services. Alopecia has several causes; one of which is due to tension on the scalp secondary to tight hairstyles. In the U.S., alopecia has a lifetime prevalence of 1.7-2.1%; no previous studies which evaluated this condition in service women were found. MATERIALS AND METHODS: We used the Military Health System Data Repository to perform a retrospective study to assess the prevalence of alopecia in ADSW from fiscal years (FYs) 2010 to 2019. Statistical analyses included descriptive statistics on patient demographics and trend analysis on the prevalence of alopecia over the 10-year study period. RESULTS: A total of 498,219 ADSW were identified over the 10-year study period, of which 2.40% had a diagnosis of alopecia. Overall, the prevalence of alopecia decreases over the 10-year period, with two observed periods of slight increase (FY 2013 to 2014 and FY 2018 to 2019) when comparing prevalence year-to-year. Of those diagnosed, the majority were young, Black, with a senior enlisted rank, and in the U.S. Army. CONCLUSION: The prevalence of alopecia in ADSW is slightly higher than that in civilian populations and is most likely underreported. It is more commonly diagnosed in Black women than would be expected based on ratios of this population in military service. Policy changes to ensure that traction alopecia is a qualifying medical condition for Veterans Affairs disability compensation, mechanisms are in place for more specific coding in the electronic medical record, and treatment options to be covered by TRICARE are recommended. All U.S. military services should consider updating and evaluating regulations to improve the health and quality of life of ADSW.

Joint-label fusion brain atlases for dementia research in Down syndrome.

Research suggests a link between Alzheimer's Disease in Down Syndrome (DS) and the overproduction of amyloid plaques. Using Positron Emission Tomography (PET) we can assess the in-vivo regional amyloid load using several available ligands. To measure amyloid distributions in specific brain regions, a brain atlas is used. A popular method of creating a brain atlas is to segment a participant's structural Magnetic Resonance Imaging (MRI) scan. Acquiring an MRI is often challenging in intellectually-imparied populations because of contraindications or data exclusion due to significant motion artifacts or incomplete sequences related to general discomfort. When an MRI cannot be acquired, it is typically replaced with a standardized brain atlas derived from neurotypical populations (i.e. healthy individuals without DS) which may be inappropriate for use in DS. In this project, we create a series of disease and diagnosis-specific (cognitively stable (CS-DS), mild cognitive impairment (MCI-DS), and dementia (DEM-DS)) probabilistic group atlases of participants with DS and evaluate their accuracy of quantifying regional amyloid load compared to the individually-based MRI segmentations. Further, we compare the diagnostic-specific atlases with a probabilistic atlas constructed from similar-aged cognitively-stable neurotypical participants. We hypothesized that regional PET signals will best match the individually-based MRI segmentations by using DS group atlases that aligns with a participant's disorder and disease status (e.g. DS and MCI-DS). Our results vary by brain region but generally show that using a disorder-specific atlas in DS better matches the individually-based MRI segmentations than using an atlas constructed from cognitively-stable neurotypical participants. We found no additional benefit of using diagnose-specific atlases matching disease status. All atlases are made publicly available for the research community. Highlight: Down syndrome (DS) joint-label-fusion atlases provide accurate positron emission tomography (PET) amyloid measurements.A disorder-specific DS atlas is better than a neurotypical atlas for PET quantification.It is not necessary to use a disease-state-specific atlas for quantification in aged DS.Dorsal striatum results vary, possibly due to this region and dementia progression.

A meta-analysis of deep brain structural shape and asymmetry abnormalities in 2,833 individuals with schizophrenia compared with 3,929 healthy volunteers via the ENIGMA Consortium.

Schizophrenia is associated with widespread alterations in subcortical brain structure. While analytic methods have enabled more detailed morphometric characterization, findings are often equivocal. In this meta-analysis, we employed the harmonized ENIGMA shape analysis protocols to collaboratively investigate subcortical brain structure shape differences between individuals with schizophrenia and healthy control participants. The study analyzed data from 2,833 individuals with schizophrenia and 3,929 healthy control participants contributed by 21 worldwide research groups participating in the ENIGMA Schizophrenia Working Group. Harmonized shape analysis protocols were applied to each site's data independently for bilateral hippocampus, amygdala, caudate, accumbens, putamen, pallidum, and thalamus obtained from T1-weighted structural MRI scans. Mass univariate meta-analyses revealed more-concave-than-convex shape differences in the hippocampus, amygdala, accumbens, and thalamus in individuals with schizophrenia compared with control participants, more-convex-than-concave shape differences in the putamen and pallidum, and both concave and convex shape differences in the caudate. Patterns of exaggerated asymmetry were observed across the hippocampus, amygdala, and thalamus in individuals with schizophrenia compared to control participants, while diminished asymmetry encompassed ventral striatum and ventral and dorsal thalamus. Our analyses also revealed that higher chlorpromazine dose equivalents and increased positive symptom levels were associated with patterns of contiguous convex shape differences across multiple subcortical structures. Findings from our shape meta-analysis suggest that common neurobiological mechanisms may contribute to gray matter reduction across multiple subcortical regions, thus enhancing our understanding of the nature of network disorganization in schizophrenia.

Psychological Resilience in West Point Graduates: Results From a Nationally Representative Study.

Background: The purpose of this study was to examine factors associated with psychological resilience in a nationally representative sample of West Point graduates. Aims: The aims of this study were to (a) employ a dimensional approach to operationalizing psychological resilience in a trauma-exposed population that had been highly trained and educated in persisting in the face of stress, was previously unstudied, and in which we could examine correlates of resilience, (b) identify key psychosocial factors, character traits, health variables, military experiences, and coping strategies as potential correlates of psychological resilience; and (c) examine whether reported gender moderated any of these associations in this population. Methods: A nationally representative sample of 1342 West Point graduates after gender integration from classes 1980 to 2011 were surveyed. Psychological resilience was operationalized using a discrepancy-based approach in which a measure of composite psychological distress (current posttraumatic stress disorder, generalized anxiety and depression symptoms) was regressed on measures of cumulative trauma burden. A multivariable linear regression model was then employed to identify factors that were independently associated with psychological resilience scores. Results: Purpose in life (29.8% of relative variance explained [RVE]), fewer perceived negative experiences in the military (20.6% RVE), social support (9.6% RVE), and grit (9.5% RVE) were the strongest correlates of psychological resilience scores for both women and men. Time in service was positively associated with resilience in women only. Conclusion: This study identifies key correlates of psychological resilience in West Point graduates, individuals who are highly trained to persevere in the face of stress and then were trauma-exposed. Most of these factors are modifiable and can be targeted in stress prevention and treatment interventions, especially for high-stress professions such as the military, frontline health care providers, and first responders.

Converting scores between the PANSS and SAPS/SANS beyond the positive/negative dichotomy.

Previous work provided conversion equations for overall indices of positive and negative symptomatology between the Positive and Negative Syndrome Scale (PANSS) and the Scales for the Assessment of Positive/Negative Symptoms (SAPS/SANS). Our objective was to provide such conversion equations for subdomains of positive and negative symptomatology in order to better account for the diversity of symptom profiles in schizophrenia. Symptoms severity was assessed using both the PANSS and SAPS/SANS in 205 patients with schizophrenia. Two exploratory factor analyses combining items from both scales were first performed separately in the positive and negative symptom domains. Positive factors were termed 'Hallucinations', 'Delusions' and 'Disorganization', while negative factors were associated with 'Expressivity', 'Amotivation' and 'Cognition', consistent with current descriptions of symptom dimensions in schizophrenia. For each factor, linear regression analyses were conducted on 80% of the data to obtain conversion equations from the PANSS to the SAPS/SANS and vice versa. Reliability was then evaluated on the 20% remaining data, with good to excellent intra-class correlation coefficients between the original and predicted scores for all but the cognition factor. These findings show that symptom severity scores can be converted with good accuracy between clinical scales beyond the positive/negative symptom dichotomy.

Perceptions of Gender and Race Equality in Leadership and Advancement Among Military Family Physicians.

INTRODUCTION: There is increasing interest in assessing gender and race-based disparities in academic medicine and healthcare leadership in civilian medicine and the U.S. Military Health System. Approximately 15% of U.S. active duty service members are women, and racial minorities are 30% of the total active duty force. This study evaluates the following factors among uniformed services family physicians: gender and race representation in attaining early career leadership positions during training and 2 years postresidency; perceptions regarding leadership opportunities and career advancement. METHODS: Registered attendees (n = 300) of the 2016 Uniformed Services Academy of Family Physicians Annual Meeting were given a voluntary and anonymous online questionnaire. The main outcomes measured were early leadership assignments and perceptions about command/leadership support, gender roles in leadership assignment, confidence to achieve leadership goals, and being passed over for leadership positions. RESULTS: Sixty-eight percent of registered attendees completed the study questionnaire. Statistically significant results, adjusting for service, grade, race, and gender, were that non-Caucasian family physicians were less likely to be chief residents (odds ratio 0.23, 95% CI 0.01-1.00) and less likely to have leadership positions within 2 years postresidency (odds ratio 0.30, 95% CI 0.10-0.91). Female family physicians were more likely to agree that gender has a role in assigning leadership positions (odds ratio 2.33, 95% CI 1.01-5.39). There were no differences in perceptions of command support for leadership; confidence in achieving desired leadership level; or in being passed over for leadership positions. CONCLUSIONS: This study provides important information about perceived gender and race equality among uniformed services family physicians. Key findings included that non-Caucasian military family physicians were less likely to attain junior leadership positions or be assigned to academic settings; and female respondents were more likely to agree that gender has a role in assignment of leadership positions. Evaluating composite personnel records of services' family physicians would provide invaluable information to complement this study.

Down syndrome: Distribution of brain amyloid in mild cognitive impairment.

INTRODUCTION: Down syndrome (DS) is associated with a higher risk of dementia. We hypothesize that amyloid beta (Aß) in specific brain regions differentiates mild cognitive impairment in DS (MCI-DS) and test these hypotheses using cross-sectional and longitudinal data. METHODS: 18F-AV-45 (florbetapir) positron emission tomography (PET) data were collected to analyze amyloid burden in 58 participants clinically classified as cognitively stable (CS) or MCI-DS and 12 longitudinal CS participants. RESULTS: The study confirmed our hypotheses of increased amyloid in inferior parietal, lateral occipital, and superior frontal regions as the main effects differentiating MCI-DS from the CS groups. The largest annualized amyloid increases in longitudinal CS data were in the rostral middle frontal, superior frontal, superior/middle temporal, and posterior cingulate cortices. DISCUSSION: This study helps us to understand amyloid in the MCI-DS transitional state between cognitively stable aging and frank dementia in DS. The spatial distribution of Aß may be a reliable indicator of MCI-DS in DS.

Career Satisfaction of Military Medical Officers.

INTRODUCTION: Having a mentor is associated with higher job satisfaction among U.S. physicians. The objective of this study was to assess satisfaction among military medical officers and to assess if mentorship and job satisfaction are associated with intention to continue military service. MATERIALS AND METHODS: This is a cross-sectional study using voluntary, anonymous data from 2018 Uniformed Services Academy of Family Physicians Annual Meeting registered attendees who completed an online Omnibus Survey. Outcome measures: satisfaction with work hours and workload; voice in organizational decision-making; amount of teaching, research, and other administrative tasks; being and having a mentor; and likelihood of remaining in the military beyond current service obligation. Statistical analysis: descriptive statistics, chi-square, and logistic regression. RESULTS: There was a 66% response rate (310/568) among registered attendees. Respondents reported being satisfied with work hours-workload (53.3%), voice in organizational decision-making (47.4%), and amount of teaching-research-other administrative tasks (55.7%). About 64.6% of respondents reported being a mentor, and 80.7% reported having a mentor. About 53.4% reported being likely/very likely to continue military service beyond their current service obligation. Adjustment for demographic and occupational factors, with significance defined as P ≤ 0.05, revealed that higher percent time in clinical care was negatively associated with satisfaction with voice in organizational decision-making; being a mentor and working in an academic practice setting were positively associated with satisfaction in amount of time with teaching, research, and administrative tasks; and having a mentor was the only factor associated with being likely/very likely to continue military service beyond current service obligation (odd ratio 3.9, 95% confidence interval 1.2-12.1). CONCLUSIONS: Having a mentor was the only factor associated with intention to remain in the military among 2018 Uniformed Services Academy of Family Physicians Omnibus Survey respondents. These results support enhancing mentorship among military medical officers.